In order to understand the involvement of beta-endorphin in the development of obesity, beta-endorphin immunoreactivity was studied in genetically obese male and female mice (C57B1/SJ ob/ob) and their lean littermate controls (plus/?). At three month's of age, the beta-endorphin immunoreactivity in pituitary glands of female obese mice is significantly greater than that of female lean controls. No such difference was observed in male obese and control mice. Since both sexes at three months of age have displayed obvious obesity, the results suggest that increased beta-endorphin may not be directly involved in the development of obesity. The results further suggest that beta-endorphin synthesis in obese mice may be modulated by sex hormones.